title: Specimen pooling for efficient use of biospecimens in studies of time to a common event.
abstract: For case-control studies that rely on expensive assays for biomarkers, specimen pooling offers a cost-effective and efficient way to estimate individual-level odds ratios. Pooling helps to conserve irreplaceable biospecimens for the future, mitigates limit-of-detection problems, and enables inclusion of individuals who have limited available volumes of biospecimen. Pooling can also allow the study of a panel of biomarkers under a fixed assay budget. Here, we extend this method for application to discrete-time survival studies. Assuming a proportional odds logistic model for risk of a common outcome, we propose a design strategy that forms pooling sets within those experiencing the outcome at the same event time. We show that the proposed design enables a cost-effective analysis to assess the association of a biomarker with the outcome. Because the standard likelihood is slightly misspecified for the proposed pooling strategy under a nonnull biomarker effect, the proposed approach produces slightly biased estimates of exposure odds ratios. We explore the extent of this bias via simulations and illustrate the method by revisiting a data set relating polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene to time to pregnancy.
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA. paramita.sahachaudhuri@duke.edu
authors.forename: Paramita
authors.initials: P
authors.lastname: Saha-Chaudhuri
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Weinberg
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D003362:Cost-Benefit Analysis; D003633:Dichlorodiphenyl Dichloroethylene / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D016015:Logistic Models; D015233:Models, Statistical; D016017:Odds Ratio; D011078:Polychlorinated Biphenyls / Q000009:adverse effects / Q000097:blood; D011247:Pregnancy; D012307:Risk Factors; D013048:Specimen Handling / Q000191:economics / Q000379:methods*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls
keywords: discrete event time outcome; pooling; pooling for biomarker; pooling for exposure; time to pregnancy